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Aberrant resting-state functional connectivity of the globus pallidus interna in first-episode schizophrenia

Qi, Wei; Wen, Zhenfu; Chen, Jingyun; Capichioni, Gillian; Ando, Fumika; Chen, Zhe Sage; Wang, Jijun; Yoncheva, Yuliya; Castellanos, Francisco X; Milad, Mohammed; Goff, Donald C
BACKGROUND:The striatal-pallidal pathway plays an important role in cognitive control and modulation of behaviors. Globus pallidus interna (GPi), as a primary output structure, is crucial in modulating excitation and inhibition. Studies of GPi in psychiatric illnesses are lacking given the technical challenges of examining this small and functionally diverse subcortical structure. METHODS:71 medication-naïve first episode schizophrenia (FES) participants and 73 healthy controls (HC) were recruited at the Shanghai Mental Health Center. Clinical symptoms and imaging data were collected at baseline and, in a subset of patients, 8 weeks after initiating treatment. Resting-state functional connectivity of sub-regions of the GP were assessed using a novel mask that combines two atlases to create 8 ROIs in the GP. RESULTS: = 0.486, p < 0.001). CONCLUSIONS:Our results implicate striatal-pallidal-thalamic pathways in antipsychotic efficacy. If replicated, these findings may reflect failure of neurodevelopmental processes in adolescence and early adulthood that decrease functional connectivity as an index of failure of the limbic/associative GPi to appropriately inhibit irrelevant signals in psychosis.
PMID: 37716202
ISSN: 1573-2509
CID: 5593342

A systematic review of digital interventions for smoking cessation in patients with serious mental illness

Martinez Agulleiro, Luis; Patil, Bhagyashree; Firth, Joseph; Sawyer, Chelsea; Amann, Benedikt L; Fonseca, Francina; Torrens, Marta; Perez, Victor; Castellanos, Francisco Xavier; Kane, John M; Guinart, Daniel
Tobacco smoking is highly prevalent among patients with serious mental illness (SMI), with known deleterious consequences. Smoking cessation is therefore a prioritary public health challenge in SMI. In recent years, several smoking cessation digital interventions have been developed for non-clinical populations. However, their impact in patients with SMI remains uncertain. We conducted a systematic review to describe and evaluate effectiveness, acceptability, adherence, usability and safety of digital interventions for smoking cessation in patients with SMI. PubMed/MEDLINE, EMBASE, CINAHL, Web of Science, PsychINFO and the Cochrane Tobacco Addiction Group Specialized Register were searched. Studies matching inclusion criteria were included and their information systematically extracted by independent investigators. Thirteen articles were included, which reported data on nine different digital interventions. Intervention theoretical approaches ranged from mobile contingency management to mindfulness. Outcome measures varied widely between studies. The highest abstinence rates were found for mSMART MIND (7-day point-prevalent abstinence: 16-40%). Let's Talk About Quitting Smoking reported greater acceptability ratings, although this was not evaluated with standardized measures. Regarding usability, Learn to Quit showed the highest System Usability Scale scores [mean (s.d.) 85.2 (15.5)]. Adverse events were rare and not systematically reported. Overall, the quality of the studies was fair to good. Digitally delivered health interventions for smoking cessation show promise for improving outcomes for patients with SMI, but lack of availability remains a concern. Larger trials with harmonized assessment measures are needed to generate more definitive evidence and specific recommendations.
PMID: 37161690
ISSN: 1469-8978
CID: 5544552

Gender Diversity and Brain Morphology Among Adolescents

Xerxa, Yllza; White, Tonya; Busa, Samantha; Trasande, Leonardo; Hillegers, Manon H J; Jaddoe, Vincent W; Castellanos, Francisco Xavier; Ghassabian, Akhgar
IMPORTANCE:Gender-diverse youths have higher rates of mental health problems compared with the general population, as shown in both clinical and nonclinical populations. Brain correlates of gender diversity, however, have been reported only among youths with gender dysphoria or in transgender individuals. OBJECTIVE:To examine brain morphologic correlates of gender diversity among adolescents from a general pediatric population who were assigned male or female at birth, separately. DESIGN, SETTING, AND PARTICIPANTS:This cross-sectional study was embedded in Generation R, a multiethnic population-based study conducted in Rotterdam, the Netherlands. Adolescents who were born between April 1, 2002, and January 31, 2006, and had information on self-reported or parent-reported gender diversity and structural neuroimaging at ages 13 to 15 years were included. Data analysis was performed from April 1 to July 31, 2022. EXPOSURES:Gender-diverse experiences among adolescents were measured with selected items from the Achenbach System of Empirically Based Assessment forms and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults, as reported by adolescents and/or their parents. MAIN OUTCOMES AND MEASURES:High-resolution structural neuroimaging data were collected using a 3-T magnetic resonance imaging scanner (at a single site). We used linear regression models to examine differences in global brain volumetric measures between adolescents who reported gender diversity and those who did not. RESULTS:This study included 2165 participants, with a mean (SD) age of 13.8 (0.6) years at scanning. A total of 1159 participants (53.5%) were assigned female at birth and 1006 (46.5%) were assigned male at birth. With regard to maternal country of origin, 1217 mothers (57.6%) were from the Netherlands and 896 (42.4%) were from outside the Netherlands. Adolescents who reported gender diversity did not differ in global brain volumetric measures from adolescents who did not report gender diversity. In whole-brain, vertexwise analyses among adolescents assigned male at birth, thicker cortices in the left inferior temporal gyrus were observed among youths who reported gender diversity compared with those who did not. No associations were observed between gender diversity and surface area in vertexwise analyses. CONCLUSIONS AND RELEVANCE:The findings of this cross-sectional study suggest that global brain volumetric measures did not differ between adolescents who reported gender diversity and those who did not. However, these findings further suggest that gender diversity in the general population correlates with specific brain morphologic features in the inferior temporal gyrus among youths who are assigned male at birth. Replication of these findings is necessary to elucidate the potential neurobiological basis of gender diversity in the general population. Future longitudinal studies should also investigate the directionality of these associations.
PMID: 37171820
ISSN: 2574-3805
CID: 5496632

Annual Research Review: Perspectives on progress in ADHD science - from characterization to cause

Sonuga-Barke, Edmund J S; Becker, Stephen P; Bölte, Sven; Castellanos, Francisco Xavier; Franke, Barbara; Newcorn, Jeffrey H; Nigg, Joel T; Rohde, Luis Augusto; Simonoff, Emily
The science of attention-deficit/hyperactivity disorder (ADHD) is motivated by a translational goal - the discovery and exploitation of knowledge about the nature of ADHD to the benefit of those individuals whose lives it affects. Over the past fifty years, scientific research has made enormous strides in characterizing the ADHD condition and in understanding its correlates and causes. However, the translation of these scientific insights into clinical benefits has been limited. In this review, we provide a selective and focused survey of the scientific field of ADHD, providing our personal perspectives on what constitutes the scientific consensus, important new leads to be highlighted, and the key outstanding questions to be addressed going forward. We cover two broad domains - clinical characterization and, risk factors, causal processes and neuro-biological pathways. Part one focuses on the developmental course of ADHD, co-occurring characteristics and conditions, and the functional impact of living with ADHD - including impairment, quality of life, and stigma. In part two, we explore genetic and environmental influences and putative mediating brain processes. In the final section, we reflect on the future of the ADHD construct in the light of cross-cutting scientific themes and recent conceptual reformulations that cast ADHD traits as part of a broader spectrum of neurodivergence.
PMID: 36220605
ISSN: 1469-7610
CID: 5360952

Family Discordance in Gender Identification Is Not Associated with Increased Depression and Anxiety Among Trans Youth

Agulleiro, Luis Martinez; Castellanos, F. Xavier; Janssen, Aron; Baroni, Argelinda
Purpose: We examined the relationship between parent- and child-reported gender identity of the youth with internalizing symptoms in transgender and gender-diverse (TGD) youth. In addition, we investigated differences in sex assigned at birth ratios and pubertal development stages in TGD and cisgender youth. Methods: We analyzed longitudinal data from the Adolescent Brain Cognitive Development study (ABCD), corresponding to baseline and 1st-to-3rd-year follow-up interviews (n = 6030 to n = 9743, age range [9"“13]). Sociodemographic variables, self- and parent-reported gender identity, and clinical measures were collected. Results: TGD youth showed higher levels of internalizing symptoms compared with cisgender youth. However, this was not worsened by discordance in gender identification between TGD youth and parents. Over the 3-year follow-up period, the number of TGD participants increased from 0.8% (95% confidence interval (CI) [0.6"“1.0]) at baseline to 1.4% (95% CI [1.1"“1.7]) at the 3rd-year follow-up (v2 = 10.476, df = 1, false discovery rate (FDR)adjusted p = 0.00256), particularly among those assigned female at birth (AFAB) in relation to people assigned male at birth (AMAB) (AMAB:AFAB at baseline: 1:1.9 vs. AMAB:AFAB at 3rd-year follow-up: 1:4.7, v2 = 40.357, df = 1, FDR-adjusted p < 0.0001). Conclusions: TGD youth in ABCD reported higher internalizing symptoms than cisgender youth, although this was not affected by parental discordance in gender identification. A substantial increase over time in TGD children AFAB was documented. More research is needed to understand the clinical implications of these preliminary results, for which the longitudinal design of ABCD will be crucial.
ISSN: 2325-8292
CID: 5615942

A practical Alzheimer"™s disease classifier via brain imaging-based deep learning on 85,721 samples

Lu, Bin; Li, Hui Xian; Chang, Zhi Kai; Li, Le; Chen, Ning Xuan; Zhu, Zhi Chen; Zhou, Hui Xia; Li, Xue Ying; Wang, Yu Wei; Cui, Shi Xian; Deng, Zhao Yu; Fan, Zhen; Yang, Hong; Chen, Xiao; Thompson, Paul M.; Castellanos, Francisco Xavier; Yan, Chao Gan
Beyond detecting brain lesions or tumors, comparatively little success has been attained in identifying brain disorders such as Alzheimer"™s disease (AD), based on magnetic resonance imaging (MRI). Many machine learning algorithms to detect AD have been trained using limited training data, meaning they often generalize poorly when applied to scans from previously unseen scanners/populations. Therefore, we built a practical brain MRI-based AD diagnostic classifier using deep learning/transfer learning on a dataset of unprecedented size and diversity. A retrospective MRI dataset pooled from more than 217 sites/scanners constituted one of the largest brain MRI samples to date (85,721 scans from 50,876 participants) between January 2017 and August 2021. Next, a state-of-the-art deep convolutional neural network, Inception-ResNet-V2, was built as a sex classifier with high generalization capability. The sex classifier achieved 94.9% accuracy and served as a base model in transfer learning for the objective diagnosis of AD. After transfer learning, the model fine-tuned for AD classification achieved 90.9% accuracy in leave-sites-out cross-validation on the Alzheimer"™s Disease Neuroimaging Initiative (ADNI, 6,857 samples) dataset and 94.5%/93.6%/91.1% accuracy for direct tests on three unseen independent datasets (AIBL, 669 samples / MIRIAD, 644 samples / OASIS, 1,123 samples). When this AD classifier was tested on brain images from unseen mild cognitive impairment (MCI) patients, MCI patients who converted to AD were 3 times more likely to be predicted as AD than MCI patients who did not convert (65.2% vs. 20.6%). Predicted scores from the AD classifier showed significant correlations with illness severity. In sum, the proposed AD classifier offers a medical-grade marker that has potential to be integrated into AD diagnostic practice.
ISSN: 2196-1115
CID: 5350292

Cerebro-cerebellar Dysconnectivity in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Wang, Pan; Wang, Jianlin; Jiang, Yuan; Wang, Zedong; Meng, Chun; Castellanos, F Xavier; Biswal, Bharat B
OBJECTIVE:Abnormal cerebellar development has been implicated in Attention-Deficit/Hyperactivity Disorder (ADHD), although cerebro-cerebellar functional connectivity (FC) has yet to be examined in ADHD. Our objective is to investigate the disturbed cerebro-cerebellar FC in children and adolescents with ADHD. METHOD/METHODS:We analyzed the dataset of 106 individuals with ADHD (68 children, 38 adolescents) and 62 healthy comparisons (34 children, 28 adolescents) from the publicly available ADHD-200 dataset. We identified seven cerebellar sub-regions based on cerebro-cerebellar FC and subsequently obtained the FC maps of cerebro-cerebellar networks. Main effects of ADHD and age and their interaction were examined using two-way analysis of variance. RESULTS:Compared to comparisons, ADHD showed higher cerebro-cerebellar FC in superior temporal gyrus within the somatomotor network. Interactions of diagnosis and age were identified in the supplementary motor area and postcentral gyrus within the somatomotor network and middle temporal gyrus within the ventral attention network. Follow-up Pearson correlation analysis revealed decreased cerebro-cerebellar FC in these regions with increasing age in comparisons, while the opposite pattern of increased cerebro-cerebellar FC occurred in ADHD. CONCLUSION/CONCLUSIONS:Increased cerebro-cerebellar FC in superior temporal gyrus within the somatomotor network could underlie impairments in cognitive control and somatic motor function in ADHD. In addition, increasing cerebro-cerebellar FC in older participants with ADHD suggests that enhanced cerebellar involvement may compensate for dysfunctions of the cerebral cortex in ADHD.
PMID: 35661770
ISSN: 1527-5418
CID: 5236272

1.93 Testing Continued Effectiveness Through Multiple Modifications of an Empirically Supported Treatment for Organization, Time Management, and Planning Deficits in ADHD and Related Disorders [Meeting Abstract]

Gallagher, R; Haroon, M; Yoncheva, Y; Conlon, G; Abikoff, H; Castellanos, F X
Objectives: Organizational skills training (OST) for youth with ADHD is an efficacious treatment that addresses impairments at home and in school. Modifications of OST were conducted to treat children with or without ADHD, to reduce treatment barriers, and to respond to changes in school demands during the COVID-19 pandemic.
Method(s): After an initial RCT documenting OST efficacy, 3 further studies involved: 1) an open replication of the original RCT confirming improvements in organization, time management, and planning (OTMP) in children diagnosed with ADHD (N = 15) using twice-weekly in-person visits; 2) a subsequent open trial investigating children with deficient organizational skills with or without ADHD and altering delivery to involve a combination of in-person and virtual meetings (N = 29); and 3) a third study with subjects with low OTMP skills who do not necessarily have ADHD, receive treatment with combined in-person and virtual delivery or, in response to COVID-19 restrictions, fully virtual delivery (N = 27, thus far), and, in response to remote school delivery, have altered OST content to fit varied school instruction demands (eg, use of electronic documents instead of papers) while adhering to the principles of OST. Change was measured on the Children's Organizational Skills Scales (COSS).
Result(s): 1) Improvements in OTMP skills (parent ratings d = 3.73; teacher ratings d = 1.12) in the first open study were comparable to the initial RCT findings. 2) In study 2, parents also reported substantial improvements (d = 3.04), and teachers reported large changes (d = 0.88) in pre-post comparisons. 3) In the ongoing RCT, subjects who received treatment immediately were reported to have large changes by parents (d = 2.17) and moderate changes by teachers (d = 0.47) when compared to waitlist controls.
Conclusion(s): Initial analyses indicate that OST leads to OTMP improvements in children struggling with disorganization with and without ADHD diagnosis. Improvements are found when treatment is delivered fully in-person, delivered in hybrid in-person and virtual meetings, or delivered fully virtually. OST could help children with or without ADHD improve behavioral and emotional adjustment at home and in school, when treatment delivery is modified to increase treatment availability, and when school demands are varied. ADHD, CBT, EBP
ISSN: 1527-5418
CID: 5511342

Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Patel, Yash; Shin, Jean; Abé, Christoph; Agartz, Ingrid; Alloza, Clara; Alnæs, Dag; Ambrogi, Sonia; Antonucci, Linda A; Arango, Celso; Arolt, Volker; Auzias, Guillaume; Ayesa-Arriola, Rosa; Banaj, Nerisa; Banaschewski, Tobias; Bandeira, Cibele; BaÅŸgöze, Zeynep; Cupertino, Renata Basso; Bau, Claiton H D; Bauer, Jochen; Baumeister, Sarah; Bernardoni, Fabio; Bertolino, Alessandro; Bonnin, Caterina Del Mar; Brandeis, Daniel; Brem, Silvia; Bruggemann, Jason; Bülow, Robin; Bustillo, Juan R; Calderoni, Sara; Calvo, Rosa; Canales-Rodríguez, Erick J; Cannon, Dara M; Carmona, Susanna; Carr, Vaughan J; Catts, Stanley V; Chenji, Sneha; Chew, Qian Hui; Coghill, David; Connolly, Colm G; Conzelmann, Annette; Craven, Alexander R; Crespo-Facorro, Benedicto; Cullen, Kathryn; Dahl, Andreas; Dannlowski, Udo; Davey, Christopher G; Deruelle, Christine; Díaz-Caneja, Covadonga M; Dohm, Katharina; Ehrlich, Stefan; Epstein, Jeffery; Erwin-Grabner, Tracy; Eyler, Lisa T; Fedor, Jennifer; Fitzgerald, Jacqueline; Foran, William; Ford, Judith M; Fortea, Lydia; Fuentes-Claramonte, Paola; Fullerton, Janice; Furlong, Lisa; Gallagher, Louise; Gao, Bingchen; Gao, Si; Goikolea, Jose M; Gotlib, Ian; Goya-Maldonado, Roberto; Grabe, Hans J; Green, Melissa; Grevet, Eugenio H; Groenewold, Nynke A; Grotegerd, Dominik; Gruber, Oliver; Haavik, Jan; Hahn, Tim; Harrison, Ben J; Heindel, Walter; Henskens, Frans; Heslenfeld, Dirk J; Hilland, Eva; Hoekstra, Pieter J; Hohmann, Sarah; Holz, Nathalie; Howells, Fleur M; Ipser, Jonathan C; Jahanshad, Neda; Jakobi, Babette; Jansen, Andreas; Janssen, Joost; Jonassen, Rune; Kaiser, Anna; Kaleda, Vasiliy; Karantonis, James; King, Joseph A; Kircher, Tilo; Kochunov, Peter; Koopowitz, Sheri-Michelle; Landén, Mikael; Landrø, Nils Inge; Lawrie, Stephen; Lebedeva, Irina; Luna, Beatriz; Lundervold, Astri J; MacMaster, Frank P; Maglanoc, Luigi A; Mathalon, Daniel H; McDonald, Colm; McIntosh, Andrew; Meinert, Susanne; Michie, Patricia T; Mitchell, Philip; Moreno-Alcázar, Ana; Mowry, Bryan; Muratori, Filippo; Nabulsi, Leila; Nenadić, Igor; O'Gorman Tuura, Ruth; Oosterlaan, Jaap; Overs, Bronwyn; Pantelis, Christos; Parellada, Mara; Pariente, Jose C; Pauli, Paul; Pergola, Giulio; Piarulli, Francesco Maria; Picon, Felipe; Piras, Fabrizio; Pomarol-Clotet, Edith; Pretus, Clara; Quidé, Yann; Radua, Joaquim; Ramos-Quiroga, J Antoni; Rasser, Paul E; Reif, Andreas; Retico, Alessandra; Roberts, Gloria; Rossell, Susan; Rovaris, Diego Luiz; Rubia, Katya; Sacchet, Matthew; Salavert, Josep; Salvador, Raymond; Sarró, Salvador; Sawa, Akira; Schall, Ulrich; Scott, Rodney; Selvaggi, Pierluigi; Silk, Tim; Sim, Kang; Skoch, Antonin; Spalletta, Gianfranco; Spaniel, Filip; Stein, Dan J; Steinsträter, Olaf; Stolicyn, Aleks; Takayanagi, Yoichiro; Tamm, Leanne; Tavares, Maria; Teumer, Alexander; Thiel, Katharina; Thomopoulos, Sophia I; Tomecek, David; Tomyshev, Alexander S; Tordesillas-Gutiérrez, Diana; Tosetti, Michela; Uhlmann, Anne; Van Rheenen, Tamsyn; Vazquez-Bourgón, Javier; Vernooij, Meike W; Vieta, Eduard; Vilarroya, Oscar; Weickert, Cynthia; Weickert, Thomas; Westlye, Lars T; Whalley, Heather; Willinger, David; Winter, Alexandra; Wittfeld, Katharina; Yang, Tony T; Yoncheva, Yuliya; Zijlmans, Jendé L; Hoogman, Martine; Franke, Barbara; van Rooij, Daan; Buitelaar, Jan; Ching, Christopher R K; Andreassen, Ole A; Pozzi, Elena; Veltman, Dick; Schmaal, Lianne; van Erp, Theo G M; Turner, Jessica; Castellanos, F Xavier; Pausova, Zdenka; Thompson, Paul; Paus, Tomas
BACKGROUND:Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS:Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS:Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS:Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
PMID: 35489875
ISSN: 1873-2402
CID: 5217792

Exploring self-generated thoughts in a resting state with natural language processing

Li, Hui-Xian; Lu, Bin; Chen, Xiao; Li, Xue-Ying; Castellanos, Francisco Xavier; Yan, Chao-Gan
The present study seeks to examine individuals' stream of thought in real time. Specifically, we asked participants to speak their thoughts freely out loud during a typical resting-state condition. We first examined the feasibility and reliability of the method and found that the oral reporting method did not significantly change the frequency or content characteristics of self-generated thoughts; moreover, its test-retest reliability was high. Based on methodological feasibility, we combined natural language processing (NLP) with the Bidirectional Encoder Representation from Transformers (BERT) model to directly quantify thought content. We analyzed the divergence of self-generated thought content and expressions of sadness and empirically verified the validity and behavioral significance of the metrics calculated by BERT. Furthermore, we found that reflection and brooding could be differentiated by detecting the divergence of self-generated thought content and expressions of sadness, thus deepening our understanding of rumination and depression and providing a way to distinguish adaptive from maladaptive rumination. Finally, this study provides a new framework to examine self-generated thoughts in a resting state with NLP, extending research on the continuous content of instant self-generated thoughts with applicability to resting-state functional brain imaging.
PMID: 34647279
ISSN: 1554-3528
CID: 5068022